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Despite advances in understanding molecular and cellular changes in the aging nervous system, the upstream drivers of these changes remain poorly defined. Here, we investigate the roles of non-neural tissues in neuronal aging, using the cutaneous PVD polymodal sensory neuron in Caenorhabditis elegans as a model. We demonstrate that during normal aging, PVD neurons progressively develop excessive dendritic branching, functionally correlated with age-related proprioceptive deficits. Our study reveals that decreased collagen expression, a common age-related phenomenon across species, triggers this process. Specifically, loss-of-function in dpy-5 or col-120, genes encoding cuticular collagens secreted to the epidermal apical surface, induces early-onset excessive dendritic branching and proprioceptive deficits. Adulthood-specific overexpression of dpy-5 or col-120 mitigates excessive branching in aged animals without extending lifespan, highlighting their specific roles in promoting neuronal health span. Notably, collagen reduction specifically drives excessive branching in select sensory neuron subclasses but does not contribute to PVD dendritic beading, another aging-associated neurodegenerative phenotype associated with distinct mechanosensitive dysfunction. Lastly, we identify that rig-3, an immunoglobulin superfamily member expressed in interneurons, acts upstream of collagen genes to maintain PVD dendritic homeostasis during aging, with collagen's regulatory role requiring daf-16/FOXO. These findings reveal that age-related collagen reduction cues neuronal aging independently of collagen's traditional structural support function, possibly involving bi-directional communication processes between neurons and non-neuronal cells. Our study also offers new insights into understanding selective neuron vulnerability in aging, emphasizing the importance of multi-tissue strategies to address the complexities of neuronal aging.
Pubmed ID: 39731224
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Software for computational neurophysiology. Simulation environment is used for building and using computational models of neurons and networks of neurons. NEURON Users Group can participate in collaborative development of documentation, tutorials, and software.
View all literature mentionsCenter that acquires, maintains, and distributes genetic stocks and information about stocks of the small free-living nematode Caenorhabditis elegans for use by investigators initiating or continuing research on this genetic model organism. A searchable strain database, general information about C. elegans, and links to key Web sites of use to scientists, including WormBase, WormAtlas, and WormBook are available.
View all literature mentionsCaenorhabditis elegans with name col-141(gk5185) V. from WB.
View all literature mentionsCaenorhabditis elegans with name dpy-10(e128) II. from WB.
View all literature mentionsCaenorhabditis elegans with name mev-1(kn1) III. from WB.
View all literature mentionsCaenorhabditis elegans with name Caenorhabditis elegans wild isolate. from WB.
View all literature mentionsCaenorhabditis elegans with name zdIs5 I. from WB.
View all literature mentionsCaenorhabditis elegans with name zIs356[daf-16::gfp] from WB.
View all literature mentionsCaenorhabditis elegans with name dpy-5(e907) I; sEx10008. from WB.
View all literature mentionsCaenorhabditis elegans with name rig-3(ok2156) X. from WB.
View all literature mentionsCaenorhabditis elegans with name wdIs51. from WB.
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